梭曼与乙酰胆碱酯酶(AChE)受体的对接研究

根据梭曼与AChE体系的对接要求，对CVFF力场中P—F键的参数进行了修改和补充。之后运用新建的力场参数，对梭曼与AChE进行了对接研究，并实现了应用量子化学／分子力学方法ONIOM(B3LYP／6—31G(d)／／UFF)对大分子体系的计算研究。分子力学对接研究表明，新参数与原CVFF力场有较好的一致性，可以完全适应于所研究的体系。同时，通过计算得到10个低能量构象，其中两个最低构象的结构与ONIOM计算结果一致，这也表明对于研究大分子与小分子对接等过程特别是构象搜寻方面，CVFF力场仍然可以得到比较合理的结果。但ONIOM计算也显示出分子力场方法在处理受体与底物之间易发生化学反应或有化学反应产生趋势的体系时会产生误差，对强氢键的估计不足将限制其应用范围。

Docking study of soman and acetylcholinesterase

Docking of the Soman and Acetylcholinesterase(AChE) was studied by using molecular mechanics (CVFF forcefield) and two-layer molecular mechanics & quantum mechanics hybrid methods (ONIOM: B3LYP/6-31G (d)//UFF). Firstly, new parameter on P-F bond using Hartree-Fock approximation at 6-31G(d) level was established and incorporated into the CVFF forcefield in order that the forcefield could be adapted to the system. Molecular mechanic and subsequently molecular dynamic calculations affirmed the consistency of the new parameter with CVFF and finally found out 10 conformations of the binding structure. The result shows that CVFF does well on docking system of ligand and acceptor especially for conformation searching. However, later calculations conducted by ONIOM exhibited that the distance between the F atom (Soman) and the hydroxy H atom (Ser200) are much shorter than the CVFF calculations results, which also indicates that CVFF forcefield was incapable in modeling strong H-bond system, and that would limit its application scope.